Review on two-dimensional material-based field-effect transistor biosensors: accomplishments, mechanisms, and perspectives.

Field-effect transistor (FET) is regarded as the most promising candidate for the next-generation biosensor, benefiting from the advantages of label-free, easy operation, low cost, easy integration, and direct detection of biomarkers in liquid environments. With the burgeoning advances in nanotechnology and biotechnology, researchers are trying to improve the sensitivity of FET biosensors and broaden their application scenarios from multiple strategies. In order to enable researchers to understand and apply FET biosensors deeply, focusing on the multidisciplinary technical details, the iteration and evolution of FET biosensors are reviewed from exploring the sensing mechanism in detecting biomolecules (research direction 1), the response signal type (research direction 2), the sensing performance optimization (research direction 3), and the integration strategy (research direction 4). Aiming at each research direction, forward perspectives and dialectical evaluations are summarized to enlighten rewarding investigations.

Acute Kidney Failure: Current Challenges and New Perspectives.

Acute kidney failure, also called acute kidney injury (AKI), is defined by a sudden loss of kidney function that is conventionally determined on the basis of increased serum creatinine levels and reduced urinary output [...].

Factors Influencing the Level of Depression and Anxiety of Community-Dwelling Patients with Schizophrenia in China during the COVID-19 Pandemic

The coronavirus disease 2019 (COVID-19) poses a huge challenge to global public health. People with schizophrenia living in communities urgently need effective interventions to help them adjust to life and work, but they have not received enough attention. This study aims to assess the prevalence of anxiety and depression symptoms in community-dwelling patients with schizophrenia in China during the epidemic and to explore the possible influencing factors. Methods: Using a cross-sectional survey, we collected 15,165 questionnaires. Assessments included demographic information, concern about COVID-19-related information, sleep status, anxiety and depressive symptoms, and accompanying illnesses. The 7-item Generalized Anxiety Disorder (GAD-7) and the 9-item Patient Health Questionnaire (PHQ-9) were used to evaluate depression and anxiety levels. Group comparison was conducted by t-test, ANOVA, or chi-square test wherever suitable, with Bonferroni pairwise correction. Multivariate logistic regression was performed to identify predictors for anxiety and depression. Results: 16.9% of patients had at least moderate anxiety, and 34.9% had at least moderate depression. T-test showed that females scored higher on GAD-7 and PHQ-9 than males, and patients without accompanying long-standing diseases, who were not concerned about COVID-19, had lower GAD-7 and PHQ-9 scores. ANOVA showed that participants aged from 30 to 39, with higher education scored higher on GAD-7, and patients with better sleep, and having less concern about COVID-19, had lower GAD-7 and PHQ-9 scores. Regression analysis indicated that participant ages of 30–39 and 40–49 positively predicted anxiety, whereas patient ages of 30–39 years positively predicted depression. Patients with poor sleep, accompanying diseases, and concern about the COVID-19 pandemic were more likely to experience anxiety and depression. Conclusion: During the pandemic, Chinese community-dwelling patients with schizophrenia had high rates of anxiety and depression. These patients deserve clinical attention and psychological intervention, especially those with risk factors.

Factors Influencing the Level of Depression and Anxiety of Community-Dwelling Patients with Schizophrenia in China during the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) poses a huge challenge to global public health. People with schizophrenia living in communities urgently need effective interventions to help them adjust to life and work, but they have not received enough attention. This study aims to assess the prevalence of anxiety and depression symptoms in community-dwelling patients with schizophrenia in China during the epidemic and to explore the possible influencing factors. METHODS: Using a cross-sectional survey, we collected 15,165 questionnaires. Assessments included demographic information, concern about COVID-19-related information, sleep status, anxiety and depressive symptoms, and accompanying illnesses. The 7-item Generalized Anxiety Disorder (GAD-7) and the 9-item Patient Health Questionnaire (PHQ-9) were used to evaluate depression and anxiety levels. Group comparison was conducted by t-test, ANOVA, or chi-square test wherever suitable, with Bonferroni pairwise correction. Multivariate logistic regression was performed to identify predictors for anxiety and depression. RESULTS: 16.9% of patients had at least moderate anxiety, and 34.9% had at least moderate depression. T-test showed that females scored higher on GAD-7 and PHQ-9 than males, and patients without accompanying long-standing diseases, who were not concerned about COVID-19, had lower GAD-7 and PHQ-9 scores. ANOVA showed that participants aged from 30 to 39, with higher education scored higher on GAD-7, and patients with better sleep, and having less concern about COVID-19, had lower GAD-7 and PHQ-9 scores. Regression analysis indicated that participant ages of 30-39 and 40-49 positively predicted anxiety, whereas patient ages of 30-39 years positively predicted depression. Patients with poor sleep, accompanying diseases, and concern about the COVID-19 pandemic were more likely to experience anxiety and depression. CONCLUSION: During the pandemic, Chinese community-dwelling patients with schizophrenia had high rates of anxiety and depression. These patients deserve clinical attention and psychological intervention, especially those with risk factors.

Effect of extracorporeal hemoadsorption in critically ill patients with COVID-19: A narrative review.

COVID-19 has been affecting the world unprecedentedly and will remain widely prevalent due to its elusive pathophysiological mechanism and the continuous emergence of new variants. Critically ill patients with COVID-19 are commonly associated with cytokine storm, multiple organ dysfunction, and high mortality. To date, growing evidence has shown that extracorporeal hemoadsorption can exert its adjuvant effect to standard of care by regulating immune homeostasis, reducing viremia, and decreasing endotoxin activity in critically ill COVID-19 cases. However, the selection of various hemofilters, timing of initiation and termination of hemoadsorption therapy, anticoagulation management of extracorporeal circuits, identification of target subgroups, and ultimate survival benefit remain controversial. The purpose of this narrative review is to comprehensively summarize the rationale for the use of hemoadsorption in critically ill patients with COVID-19 and to gather the latest clinical evidence in this field.

Effect of Continuous Renal Replacement Therapy with the oXiris Hemofilter on Critically Ill Patients: A Narrative Review.

Critically ill patients with sepsis and severe COVID-19 are commonly characterized by a dysregulated immune response and an acute kidney injury. Continuous renal replacement therapy (CRRT) is now proposed as a promising adjuvant therapy to treat these critically ill patients by removing cytokines, pathogen-associated molecular patterns, and damage-associated molecular patterns from the blood. Although multiple hemofilters, including high-cutoff membranes, the oXiris hemofilter, the CytoSorb hemoadsorption device, and the Toraymyxin hemoperfusion cartridge, have been used in current clinical practice, the use of the oXiris hemofilter in critically ill patients is of particular interest because it is the only kind of hemofilter that can provide renal replacement therapy, remove endotoxins, and adsorb cytokines simultaneously. During the past five years, a growing body of literature has shown that CRRT with the oXiris hemofilter can improve hemodynamics and organ function and can decrease cytokines and endotoxins in both septic and COVID-19 patients. Here, we performed a narrative review to describe the development history of the oXiris hemofilter and to discuss the therapeutic effect of oXiris-CRRT on critically ill patients by searching the PubMed, Web of Science, and clinicaltrials.gov databases for articles published from inception to 8 September 2022 (updated on 1 November) with an English language restriction. We also summarized the current knowledge on anticoagulation techniques and safety concerns when delivering oXiris-CRRT sessions.

Homogeneous ensemble models for predicting infection levels and mortality of COVID-19 patients: Evidence from China

Background Persistence of long-term COVID-19 pandemic is putting high pressure on healthcare services worldwide for several years. This article aims to establish models to predict infection levels and mortality of COVID-19 patients in China. Methods Machine learning models and deep learning models have been built based on the clinical features of COVID-19 patients. The best models are selected by area under the receiver operating characteristic curve (AUC) scores to construct two homogeneous ensemble models for predicting infection levels and mortality, respectively. The first-hand clinical data of 760 patients are collected from Zhongnan Hospital of Wuhan University between 3 January and 8 March 2020. We preprocess data with cleaning, imputation, and normalization. Results Our models obtain AUC = 0.7059 and Recall (Weighted avg) = 0.7248 in predicting infection level, while AUC=0.8436 and Recall (Weighted avg) = 0.8486 in predicting mortality ratio. This study also identifies two sets of essential clinical features. One is C-reactive protein (CRP) or high sensitivity C-reactive protein (hs-CRP) and the other is chest tightness, age, and pleural effusion. Conclusions Two homogeneous ensemble models are proposed to predict infection levels and mortality of COVID-19 patients in China. New findings of clinical features for benefiting the machine learning models are reported. The evaluation of an actual dataset collected from January 3 to March 8, 2020 demonstrates the effectiveness of the models by comparing them with state-of-the-art models in prediction.

Dynamic livelihood impacts of COVID-19 on different rural households in mountainous areas of China.

BACKGROUND: The outbreak of COVID-19 pandemic has brought about severe negative livelihood consequences for rural households worldwide. However, the heterogeneity and dynamics of livelihood impacts have been under-researched. There is also lacking a livelihood assessment of the pandemic based on a whole pandemic cycle. This study aimed to investigate the dynamic and heterogeneous livelihood impacts of COVID-19 pandemic for rural households in 2020 based on a case study of Southeast China. METHODS: The pandemic in China had experienced a complete cycle from initial outbreak, to intermediate recovery and finally new normal stage in 2020. We conducted face-to-face interviews with 95 rural households randomly drawn from 2 rural villages in Xunwu County, Jiangxi Province, Southeast China. The sampled households are interviewed with a questionnaire through face-to-face surveys in February and March, 2021 to evaluate the overall livelihood impacts of the pandemic during 2020. The survey collected data on demographic and economic characteristics, governmental control measures, and effects of the COVID-19 on agricultural production, employment, income, education, and daily life. In-depth interviews are also conducted to clarify the livelihood impacts of COVID-19 on villages. RESULTS: Results showed that the pandemic tremendously caused substantially negative livelihood impacts, including decreasing household income, and disorders in daily lives. The average income loss of all survey households is 6,842 RMB, accounting for 13.01% of the total household income in 2020. Containment measures also resulted in a series of disturbances in daily lives, such as rising food price additional expenditures, travel restrictions, party restrictions, closure of schools and deceasing living standards. There is remarkable household heterogeneity in the livelihood impacts. Results also revealed that the livelihood strategies of rural households to cope with the threat of COVID-19 were different in various pandemic stages. CONCLUSION: Our findings have illustrated the severity and heterogeneity of livelihood impacts on rural households induced by COVID-19 pandemic. The dynamics of livelihood impacts is also highlighted in the study. Several policy suggestion was proposed to mitigate these negative consequences of the pandemic.

Epidemic Dynamics of Two-Pathogen Spreading for Pairwise Models

In the real world, pathogens do not exist in isolation. The transmission of one pathogen may be affected by the presence of other pathogens, and certain pathogens generate multiple strains with different spreading features. Hence, the behavior of multi-pathogen transmission has attracted much attention in epidemiological research. In this paper, we use the pairwise approximation method to formulate two-pathogen models capturing cross-immunity, super-infection, and co-infection phenomena, in which each pathogen follows a susceptible-infected-susceptible (SIS) mechanism. For each model, we calculate the basic reproduction number and analyze the stability of equilibria, and discuss the differences from the mean-field approach. We demonstrate that simulations are in good agreement with the analytical results.

Spatial variation of dissolved organic nitrogen in Wuhan surface waters: Correlation with the occurrence of disinfection byproducts during the COVID-19 pandemic.

Intensified sanitization practices during the recent coronavirus disease-2019 (COVID-19) led to the release of chlorine-based disinfectants in surface water, potentially triggering the formation of disinfection byproducts (DBPs) in the presence of dissolved organic nitrogen (DON). Thus, a comprehensive investigation of DON's spatial distribution and its association with DBP occurrence in the surface water is urgently needed. In this study, a total of 51 water samples were collected from two rivers and four lakes in May 2020 in Wuhan to explore the regional variation of nitrogen (N) species, DON's compositional characteristics, and the three classes of DBP occurrence. In lakes, 53.0% to 86.3% of N existed as DON, with its concentration varying between 0.3-4.0 mg N/L. In contrast, NO3--N was the dominant N species in rivers. Spectral analysis revealed that DON in the lakes contained higher humic and fulvic materials with higher A254, A253/A203, SUVA254, and PIII+IV/PI+II+V ratios, while rivers had higher levels of hydrophilic compounds. Trihalomethanes (THMs) were the most prevalent DBPs in the surface waters, followed by N-nitrosamines and haloacetonitriles (HANs). The levels of N-nitrosamines (23.1-97.4 ng/L) increased significantly after the outbreak of the COVID-19 pandemic. Excessive DON in the surface waters was responsible for the formation of N-nitrosamines. This study confirmed that the presence of DON in surface water could result in DBP formation, especially N-nitrosamines, when disinfectants were discharged into surface water during the COVID-19 pandemic.

Prevalence and Characteristics of Hypoxic Hepatitis in COVID-19 Patients in the Intensive Care Unit: A First Retrospective Study.

Purpose: Coronavirus disease 2019 (COVID-19) has been associated with acute liver injury in reports worldwide. But no studies to date have described hypoxic hepatitis (HH) in patients with COVID-19. We aim to identify the prevalence of and possible mechanisms of HH in COVID-19 patients in the Intensive Care Unit (ICU). Methods: This retrospective study was conducted on 51 patients with confirmed SARS-CoV-2 infection in the ICU at Zhongnan Hospital of Wuhan University from December 21, 2019, to March 11, 2020. Information on clinical features of enrolled patients was collected for analysis. Results: HH was observed in 5.88% of the ICU patients with SARS-CoV-2 infection. All HH patients were progressing to respiratory failure and peak alanine aminotransferase (ALT) values were 1665, 1414, and 1140 U/L during hospitalization, respectively. All patients with HH died as a result of the deterioration of multiple organ failure (MOF). The dynamic changes of ALT, aspartate transaminase (AST), and total bilirubin (TBIL) levels were more dramatic in HH groups. Levels of TBIL, C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6(IL-6) showed statistically significant elevation in HH cases compared with that in non-HH cases (P < 0.001). Besides, the median survival time of the HH group was significantly shorter than the non-HH group (P < 0.05). Conclusions: In ICU, HH was not a rare condition in patients with severe COVID-19 and has a high mortality. The main causes of HH are respiratory and cardiac failure and may be associated with the immune-mediated inflammatory response. Clinicians should search for any underlying hemodynamic or respiratory instability even in patients with normal ALT levels on admission.

[Effectiveness of convalescent plasma for treatment of coronavirus disease 2019 patients].

OBJECTIVE: To evaluate the effectiveness and safety of convalescent plasma therapy in patients with severe and critical coronavirus disease 2019 (COVID-19). METHODS: Plasma of 200-400 mL was collected from convalescent patients 2 weeks after being discharged from the hospital. After viral nucleic acid testing and antibody testing, the plasma was infused into 16 severe or critical COVID-19 patients. Time for viral nucleic acid amplification (NAA) test turning negative, total volume of plasma transfusion, average antibody concentration, and total antibody amount were recorded. White blood cell (WBC) counts, lymphocyte (LYM) counts, neutrophil (NEU) counts, alanine aminotransferase (ALT), aspartate aminotransferase (AST), C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme (CK-MB), hypersensitive cardiac troponin T (hs-cTnT), and lactic acid (Lac) levels were measured and the rate of change was calculated at the baseline (d0) before plasma transfusion, and day 1 (d1), day 3 (d3) after transfusion. RESULTS: (1) Patient characteristics: among the 16 patients, 5 cases (31.25%) were severe COVID-19, and 11 cases (68.75%) were critical COVID-19; 62.50% (10/16) of the patients had primary disease; the percentage of invasive ventilation and use of extracorporeal membrane pulmonary oxygenation (ECMO) in critical patients were 90.91% (10/11) and 45.46% (5/11) respectively. (2) Antibody concentration of convalescent plasma and time for NAA test turning negative: the convalescent plasma antibody concentration in this study was ranged from 10.93 kAU/L to 114.7 kAU/L, with an average value of (56.44±39.40) kAU/L. NAA test was continuously positive before plasma transfusion in 10 patients, and the time for NAA test turning negative could be counted. Eight patients turned negative from day 2 to day 8 after transfusion. Severe patients showed a shorter time for NAA test turning negative than critical patients after transfusion [2 (2-3) vs. 5 (3-8), P = 0.036]. Two critical patients transfused plasma with lower antibody concentration remained a positive result of NAA test, and died on the 3rd and 6th day respectively. (3) Laboratory results: the change rates of WBC (0.81±0.28 vs. 1.00) and NEU (0.75±0.33 vs. 1.00) were significantly decreased at d1 after convalescent plasma treatment (both P < 0.05), and the CRP level decreased to about 63% of that before transfusion (P = 0.017). No adverse events were observed during convalescent plasma transfusion. CONCLUSIONS: Viral NAA test of most patients with COVID-19 who received convalescent plasma transfusion turned negative from day 2 to day 8 after transfusion, and the turning time of severe patients was shorter than that of critical patients. Convalescent plasma therapy can reduce the patients' CRP level, and no adverse events were found during the treatment. The antibody concentration in the convalescent plasma may be one of the factors that affect the time for the nucleic acid turning negative after transfusion. Detection and screening convalescent plasma of high-titer antibody and early application to severe and critical patients are expected to improve the efficacy of convalescent plasma.

Corona Virus Disease 2019 patients with different disease severity or age range: A single-center study of clinical features and prognosis.

This study aimed to describe clinical characteristics and prognosis of Corona Virus Disease 2019 (COVID-19) patients, and to compare these features among COVID-19 patients with different disease severity or age range.Totally, 129 COVID-19 patients were retrospectively enrolled, and the information about demographics, comorbidities, medical histories, clinical symptoms, and laboratory findings at the time of hospital admission were collected. Meanwhile, their clinical outcomes were recorded. According to the fourth version of the guidelines on the Diagnosis and Treatment of COVID-19 by the National Health Commission of China, patients were divided into subgroups according to disease severity (moderate and severe/critical) or age (<40 years, 40-64 years and ≥65 years).In total patients, the most common clinical symptoms were fever and cough (all incidences over 50%). Other common clinical symptoms included tiredness/anorexia, shortness of breath, dyspnea, aching pain, expectoration, diarrhea, shivering, and nausea/vomiting. The mortality rate was 5.4%, and the median value of hospital stay was 16.0 (11.0-23.0) days. Subgroup analyses disclosed that severe/critical patients exhibited increased neutrophil count, neutrophils, C-reactive protein, calcitonin, alpha-hydroxybutyric dehydrogenase, lactate dehydrogenase, aspartate aminotransferase, gamma-glutamyl transferase, creatinine, and D-dimer levels, and more deaths compared with that in moderate patients. Regarding age, it correlated with more common fever, higher levels of red blood cell, neutrophil count, lymphocyte count, neutrophils, red cell volume distribution width standard deviation-coefficient of variation, calcitonin, alpha-hydroxybutyric dehydrogenase, Creatine Kinase, aspartate aminotransferase, gamma-glutamyl transferase, and D-dimer, raised death rate and prolonged hospital stay.Our findings provide valuable evidence regarding clinical characteristics and prognosis of COVID-19 patients to help with the understanding of the disease and prognosis improvement.

MDM2-Mediated Ubiquitination of Angiotensin-Converting Enzyme 2 Contributes to the Development of Pulmonary Arterial Hypertension.

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) converts angiotensin II, a potent vasoconstrictor, to angiotensin-(1-7) and is also a membrane protein that enables coronavirus disease 2019 (COVID-19) infectivity. AMP-activated protein kinase (AMPK) phosphorylation of ACE2 enhances ACE2 stability. This mode of posttranslational modification of ACE2 in vascular endothelial cells is causative of a pulmonary hypertension (PH)-protective phenotype. The oncoprotein MDM2 (murine double minute 2) is an E3 ligase that ubiquitinates its substrates to cause their degradation. In this study, we investigated whether MDM2 is involved in the posttranslational modification of ACE2 through its ubiquitination of ACE2, and whether an AMPK and MDM2 crosstalk regulates the pathogenesis of PH. METHODS: Bioinformatic analyses were used to explore E3 ligase that ubiquitinates ACE2. Cultured endothelial cells, mouse models, and specimens from patients with idiopathic pulmonary arterial hypertension were used to investigate the crosstalk between AMPK and MDM2 in regulating ACE2 phosphorylation and ubiquitination in the context of PH. RESULTS: Levels of MDM2 were increased and those of ACE2 decreased in lung tissues or pulmonary arterial endothelial cells from patients with idiopathic pulmonary arterial hypertension and rodent models of experimental PH. MDM2 inhibition by JNJ-165 reversed the SU5416/hypoxia-induced PH in C57BL/6 mice. ACE2-S680L mice (dephosphorylation at S680) showed PH susceptibility, and ectopic expression of ACE2-S680L/K788R (deubiquitination at K788) reduced experimental PH. Moreover, ACE2-K788R overexpression in mice with endothelial cell-specific AMPKα2 knockout mitigated PH. CONCLUSIONS: Maladapted posttranslational modification (phosphorylation and ubiquitination) of ACE2 at Ser-680 and Lys-788 is involved in the pathogenesis of pulmonary arterial hypertension and experimental PH. Thus, a combined intervention of AMPK and MDM2 in the pulmonary endothelium might be therapeutically effective in PH treatment.

The association between markers of liver injury and clinical outcomes in patients with COVID-19 in Wuhan.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) is a critical challenge for public health. The effect of COVID-19 on liver injury has not been fully established. AIMS: To evaluate the dynamic changes in liver function and the relationship between liver damage and prognosis in patients with COVID-19. METHODS: Retrospective analysis of clinical data of 675 patients with COVID-19 in Zhongnan Hospital of Wuhan University from January 3 to March 8, 2020. Patients were classified as having normal or abnormal liver function and liver injury. RESULTS: Of 675 patients, 253 (37.5%) had abnormal liver function during hospitalisation, and 52 (7.7%) had liver injury. The dynamic changes of ALT and AST levels were more significant in patients with liver injury and in those who died. AST >3-fold upper limit of normal (ULN) had the highest risk of death and mechanical ventilation. Compared to patients with normal AST levels, mortality and risk of mechanical ventilation significantly increased 19.27-fold (95% confidence interval [CI], 4.89-75.97; P < 0.0001) and 116.72-fold (95% CI, 31.58-431.46; P < 0.0001), respectively, in patients with AST above 3-fold ULN. Increased leucocytes, decreased lymphocytes and female sex were independently associated with liver injury. CONCLUSIONS: The dynamic changes in liver function may have a significant correlation with the severity and prognosis of COVID-19. Increased index of liver injury was closely related to mortality and need for mechanical ventilation. Therefore, these indicators should be closely monitored during hospitalisation.